The molecular biology of carcinogenesis.

Carcinogenesis may result from the action of any one or a combination of chemical, physical, biologic, and/or genetic insults to cells. The process of carcinogenesis may be divided into at least three stages: initiation, promotion, and progression. The first stage of carcinogenesis, initiation, results from an irreversible genetic alteration, most likely one or more simple mutations, transversions, transitions, and/or small deletions in DNA. The reversible stage of promotion does not involve changes in the structure of DNA but rather in the expression of the genome mediated through promoter-receptor interactions. The final irreversible stage of progression is characterized by karyotypic instability and malignant growth. Critical molecular targets during the stages of carcinogenesis include proto-oncogenes, cellular oncogenes, and tumor suppressor genes, alterations in both alleles of the latter being found only in the stage of progression. Although many of these critical target genes have been identified, the ultimate number and characteristics of molecular alterations that define neoplasia have not been elucidated.